Treatment admissions for cannabis-related problems have more than doubled since the mid 1990's. Clinical trials indicate that a majority of those who enter treatment for cannabis problems relapse, and relapse rates are comparable to those observed for other drugs of abuse. Currently there are no accepted pharmacotherapies for treating cannabis dependence. Administration of dronabinol (oral THC) has been shown to significantly attenuate cannabis withdrawal symptoms and the acute effects of smoked cannabis in prior studies. These effects suggest that dronabinol might be a useful adjunct intervention for treating cannabis dependence. However, only one study to date has specifically compared multiple doses of dronabinol on outcomes that are important for assessing clinical efficacy. Moreover, there is a relative dearth of data regarding the cognitive, psychomotor, and subjective side effects of chronic dronabinol administration in regular cannabis users. Specific aims of the proposed research are to replicate and extend research on the effects of dronabinol on cannabis withdrawal severity, cognitive and psychomotor performance, the acute effects of smoked cannabis, and cannabis self-administration. Experiment 1 will carefully study the dose effects of dronabinol (placebo, 10, 20, 40mg t.i.d.) in daily cannabis users. Using a within subjects design, participants will alternate between periods of ad-libitum cannabis smoking and periods of cannabis abstinence with dronabinol maintenance. Cannabis withdrawal severity, performance on a comprehensive battery of state-of-the-art cognitive and psychomotor tests, response to smoked cannabis, and ratings of medication side effects will be assessed at multiple timepoints. Experiment 2 will study the effects of dronabinol (placebo, 20, 40mg t.i.d.) on cannabis self-administration behavior during ad-libitum and restricted access choice tests. Participants will be maintained on each dronabinol dose condition in 3 counterbalanced periods lasting 12 days each. Within each of these periods, cannabis use behavior will be assessed during randomly periods of 1) ad-libitum cannabis access, and 2) restricted access during which participants must make discrete choices between smoking cannabis or receiving variable amounts of money. Placebo and active cannabis conditions will be included in order to help interpret and assess the validity of outcomes. These two experiments will extend the current knowledge of the behavioral pharmacology of dronabinol in cannabis users and will help inform whether, and at what doses, dronabinol should be considered for clinical use in the treatment of cannabis use disorders. PUBLIC HEALTH RELEVANCE: The number of people seeking treatment for marijuana-related problems is on the rise, yet there is no currently accepted medication proven to help them quit. This research is designed to determine whether the FDA approved medication dronabinol (Marinol(R)) has effects that might help make it easier for people to stop daily marijuana use, and to carefully study the occurance of safety risks and side-effects at different doses of the drug.